18F-Fluciclovine PET/CT to Distinguish Radiation Necrosis From Tumor Progression in Brain Metastases Treated With Stereotactic Radiosurgery: Results of a Prospective Pilot Study

Abstract

Purpose/Objective(s)To report results from a prospective pilot study evaluating the use of 18F Fluciclovine PET CT to distinguish radiation necrosis (RN) from tumor progression (TP) among patients (pts) with brain metastases (BM) treated with stereotactic radiosurgery (SRS).Materials/MethodsThe primary objective was to estimate the accuracy of 18F Fluciclovine PET CT in distinguishing RN from TP. The trial included adults with BM who underwent SRS and presented with a follow up MRI brain (with DSC MR perfusion) which was equivocal for RN versus TP. Within 30 days of equivocal MRI brain, pts underwent an 18F Fluciclovine PET CT (Siemens mCT) acquired 5-15 min post-injection with images generated by PSF reconstruction. Quantitative metrics for each lesion were documented and lesion to normal brain SUVmean ratios were calculated. The reference standard for diagnosis of RN vs TP was clinical follow up with MRI brain every 2-4 months until multidisciplinary consensus or tissue confirmation.ResultsOf 16 pts enrolled between 7/2019-11/2020, 1 pt died prior to diagnosis, allowing 15 evaluable subjects with 20 lesions. Primary histology was NSCLC in 9 (45%) lesions, breast in 7 (35%), melanoma in 3 (15%), and endometrial in 1 (5%). The final diagnosis was RN in 16 (80%) lesions and TP in 4 (20%). SUVmax was a statistically significant predictor of TP (P = 0.011), with higher SUVmax values indicative of TP. The area under the ROC curve was 0.833 (95% CI: 0.590, 1.0). A cutoff of 4.3 provided a sensitivity to identify TP of 1.0 (4/4) and specificity to rule out TP of 0.63 (10/16). Additional quantitative metrics are summarized in Table 1. SUVmean (P = 0.018), SUVpeak (P = 0.007), and SUVpeak/normal (P = 0.002) reached statistical significance as predictors of TP. SUVmax/normal (P = 0.1) and SUVmean/normal (P = 0.5) were not statistically significant. The AUC for SUVmax was not significantly higher than the AUCs for the other quantitative variables (P-values > 0.2).ConclusionIn this prospective pilot study, 18F Fluciclovine PET CT demonstrated promising accuracy to distinguish RN from TP among pts with BM previously treated with SRS. Using SUVmax, a cutpoint of 4.3 provided a sensitivity of 1.0 and specificity of 0.63. Confirmatory phase II and III studies are ongoing. To report results from a prospective pilot study evaluating the use of 18F Fluciclovine PET CT to distinguish radiation necrosis (RN) from tumor progression (TP) among patients (pts) with brain metastases (BM) treated with stereotactic radiosurgery (SRS). The primary objective was to estimate the accuracy of 18F Fluciclovine PET CT in distinguishing RN from TP. The trial included adults with BM who underwent SRS and presented with a follow up MRI brain (with DSC MR perfusion) which was equivocal for RN versus TP. Within 30 days of equivocal MRI brain, pts underwent an 18F Fluciclovine PET CT (Siemens mCT) acquired 5-15 min post-injection with images generated by PSF reconstruction. Quantitative metrics for each lesion were documented and lesion to normal brain SUVmean ratios were calculated. The reference standard for diagnosis of RN vs TP was clinical follow up with MRI brain every 2-4 months until multidisciplinary consensus or tissue confirmation. Of 16 pts enrolled between 7/2019-11/2020, 1 pt died prior to diagnosis, allowing 15 evaluable subjects with 20 lesions. Primary histology was NSCLC in 9 (45%) lesions, breast in 7 (35%), melanoma in 3 (15%), and endometrial in 1 (5%). The final diagnosis was RN in 16 (80%) lesions and TP in 4 (20%). SUVmax was a statistically significant predictor of TP (P = 0.011), with higher SUVmax values indicative of TP. The area under the ROC curve was 0.833 (95% CI: 0.590, 1.0). A cutoff of 4.3 provided a sensitivity to identify TP of 1.0 (4/4) and specificity to rule out TP of 0.63 (10/16). Additional quantitative metrics are summarized in Table 1. SUVmean (P = 0.018), SUVpeak (P = 0.007), and SUVpeak/normal (P = 0.002) reached statistical significance as predictors of TP. SUVmax/normal (P = 0.1) and SUVmean/normal (P = 0.5) were not statistically significant. The AUC for SUVmax was not significantly higher than the AUCs for the other quantitative variables (P-values > 0.2). In this prospective pilot study, 18F Fluciclovine PET CT demonstrated promising accuracy to distinguish RN from TP among pts with BM previously treated with SRS. Using SUVmax, a cutpoint of 4.3 provided a sensitivity of 1.0 and specificity of 0.63. Confirmatory phase II and III studies are ongoing.